Scroll up
Top
LLT Considerations

Statins are central to therapy, but not the whole picture1

Statins play a central role in lowering cholesterol. Still, they may not be enough for every patient, underscoring the importance of complementary, lipid-lowering therapies (LLTs).1
Jump to:
Efficacy/Dose TitrationLLT LimitationsMinimizing Risk of DiabetesAdmin/Tolerability
Efficacy/Dose Titration

Low-density lipoprotein cholesterol (LDL-C) reduction efficacy

Lipid-lowering agent1
High-intensity statins
Low- or moderate-intensity statins
Typical LDL-C reduction (%)1
50%
<30 to 49%

Dose titration

Doubling the statin dose results in an incremental LDL-C reduction of only 6%2

Horizontal dose titration graphicHorizontal dose titration graphic
LLT Limitations

While statins can lower LDL-C; other lipid risks can remain

Statins lower LDL-C, but effects on other lipid-related risk-enhancing factors are limited.4,5

When looking at LDL-C and beyond, statins impact different lipid-related risk-enhancers in distinct ways4,5:
Lp(a)
May increase with statin therapy (commonly ~10–20%, up to ~30% in some studies)6,7
HDL-C
Modest, dose-dependent, and variable increases due to the types of statins 
(≈1–10%)10,11
sdLDL-P
LDL-C reductions are driven largely by decreases in larger LDL subfractions; sdLDL-P reductions are modest, and the LDL particle-size distribution can shift toward smaller diameters8,9

Lp(a), lipoprotein(a); HDL-C, high-density lipoprotein cholesterol; sdLDL-P, small dense low-density lipoprotein particles.

Minimizing Risk of Diabetes

Statin use can increase the risk of new-onset diabetes and diabetes progression12

In a meta-analysis of 19 double-blind trials with a total of 123,940 patients treated with statin or placebo.12

High intensity statin therapy was associated with a 36% increased risk of new-onset diabetes.

Low or moderate-intensity statin therapy was associated with a 10% increased risk of new-onset diabetes.

In a separate cohort study of 83,022 matched pairs of patients with diabetes, statin use was associated with a 37% increased relative risk of diabetes progression.13

  • 16% higher risk of insulin initiation
  • 41% higher risk of new classes of glucose-lowering medication
  • 13% higher risk of persistent hyperglycemia
  • 24% higher risk of ketoacidosis or uncontrolled diabetes
Admin/Tolerability

Route of administration

Current injectable therapies face significant patient barriers.14

Needle fear affects medication uptake for ≈15% of adult patients.15

Patient tolerability remains a concern

Although statin therapy remains the standard of care, many patients cannot tolerate optimal doses.16

Skeletal muscle-related symptoms reported as muscle soreness, aches, cramps, fatigue, and/or weakness. Myopathy and rhabdomyolysis are rare.16

Confusion and memory loss are associated with statin intolerance.16

Use of statin therapy is associated with increased liver transaminase levels.16

Statin-associated muscle symptoms are often reported after a statin dose increase.17

Up to 30% of patients are partially or completely statin intolerant.16 Statin intolerance can occur at any time during therapy.18

Side effects of medication—both feared and experienced—are common reasons patients decline and discontinue statins.16

Register to receive updates from NewAmsterdam Pharma

Contact Us

References: 1. Michaeli DT, Michaeli JC, Albers S, Boch T, Michaeli T. Established and emerging lipid-lowering drugs for primary and secondary cardiovascular prevention. Am J Cardiovasc Drugs. 2023;23(5):477-495. doi:10.1007/s40256-023-00594-5 2. Clem JR, Strain JD, Farver DK. Individualized initiation of statin therapy determined by baseline LDL-C: Are you more likely to achieve goal LDL-C? Risk Manag Healthc Policy. 2010;3:1-11. doi:10.2147/RMHP.S7376 3. Nodari S, Rocca P, Saporetti A, et al. The combination of ezetimibe and statin: a new treatment for hypercholesterolemia. Heart Int. 2007;3(1):12-17. doi:10.4081/hi.2007.12 4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143. doi:10.1161/CIR.0000000000000625 5. Reijnders E, van der Laarse A, Jukema JW, Cobbaert CM. High residual cardiovascular risk after lipid-lowering: prime time for predictive, preventive, personalized, participatory, and psycho-cognitive medicine. Front Cardiovasc Med. 2023;10:1264319. doi:10.3389/fcvm.2023.1264319 6. Duarte Lau F, Giugliano RP. Lipoprotein(a) and its significance in cardiovascular disease: a review. JAMA Cardiol. 2022;7(7):760–769. doi:10.1001/jamacardio.2022.0987 7. Tsimikas S, Fazio S, Ferdinand KC, et al. Lipoprotein(a) reduction in persons with cardiovascular disease. N Engl J Med. 2020;382(3):244-255. doi:10.1056/NEJMoa1905239 8. Mora S, Caulfield MP, Wohlgemuth J, et al. Atherogenic lipoprotein subfractions determined by ion mobility and first cardiovascular events after random allocation to high-intensity statin or placebo: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Circulation. 2015;132(23):2220-2229. doi:10.1161/CIRCULATIONAHA.115.016857 9. Choi CU, Seo HS, Lee EM, et al. Statins do not decrease small, dense low-density lipoprotein. Tex Heart Inst J. 2010;37(4):421-428. 10. Mach F, Baigent C, Catapano AL, et al; ESC Scientific Document Group. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455 11. Barter PJ, Brandrup-Wognsen G, Palmer MK, Nicholls SJ. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database. J Lipid Res. 2010;51(6):1546-1553. doi:10.1194/jlr.P002816 12. Cholesterol Treatment Trialists’ (CTT) Collaboration. Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Lancet Diabetes Endocrinol. 2024;12(5):306-319. doi:10.1016/S2213-8587(24)00040-8 13. Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA. Association of statin therapy initiation with diabetes progression: a retrospective matched-cohort study. JAMA Intern Med. 2021;181(12):1562-1574. doi:10.1001/jamainternmed.2021.5714 14. Gu J, Sanchez R, Chauhan A, Fazio S, Wong N. Lipid treatment status and goal attainment among patients with atherosclerotic cardiovascular disease in the United States: a 2019 update. Am J Prev Cardiol. 2022;10:100336. doi:10.1016/j.ajpc.2022.100336 15. McLenon J, Rogers MAM. The fear of needles: a systematic review and meta-analysis. J Adv Nurs. 2019;75(1):30-42. doi:10.1111/jan.13818 16. Cheeley MK, Saseen JJ, Agarwala A, et al. NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient. J Clin Lipidol. 2022;16(4):361-375. doi:10.1016/j.jacl.2022.05.068 17. Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395-2410. doi:10.1016/j.jacc.2016.02.071 18. Bui A, Kwon J, Kim J, Lucas A. Overcoming barriers to statin adherence. US Pharm. 2019;44(6):19-22.